The relationship between cellular metabolite levels and neuronal transmission is being investigated in the in vitro hippocampus. Currently, the concentrations of the adenylates, phosphocreatine, creatine, lactate, GABA and the cyclic nucleotides are evaluated for slices during in vivo and in vitro ischemia (up to 15 minutes) or an ensuing in vitro recovery period. The magnitude of the evoked field potential is also recorded. There is, as yet, no clear relationship between the recovery of neuronal transmission and the return to steady-state of any of the metabolites following ischemia. Of additional interest is the fall in total adenylate levels, energy charge and phosphocreatine in vitro compared to in vivo levels. Thus, the initial decapitation-induced ischemia irreversibly alters the metabolic profile of the in vitro hippocampus. The presence of the evoked response indicates that these marked changes are compatible with neural funcion. Subsequent in vitro ischemic episodes produce transient changes in the metabolite levels which are reversible to the new steady-state distribution. These in vitro ischemic changes are compared to those observed in vivo.